HIV Infections Clinical Trial
— UZ-CHS-BCOfficial title:
HIV Exposure, Disease Acquisition and Progression Among Children: Role of Maternal Immunogenetics, Viral Genetic Diversity, HAART Exposure, Co-morbidities and Psycho-Social Status: (UZ-CHS Birth Cohort)
Verified date | November 2020 |
Source | University of Zimbabwe |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
Background Commencement of lifelong highly active antiretroviral therapy (HAART) immediately after HIV diagnosis (option B+), for treatment of human immunodeficiency virus (HIV), has greatly improved maternal-infant health in sub Saharan Africa (SSA). However, this development has also dramatically increased the number of maternally HAART/HIV-exposed-uninfected (HEU) infants in areas of high HIV prevalence. Compared to their HIV-unexposed uninfected (HUU) counterparts, HEU infants show increased mortality, higher rates of adverse birth outcomes, infectious and non-communicable diseases and impaired growth, immune responses and neurodevelopment. Adverse clinical outcomes and their respective risk factors alongside associated biomarkers of HEU infants in SSA have been insufficiently characterized. Early exposure to HAART and HIV might be risk factors for the adverse outcomes in HEU infants but other potential risk factors and biomarkers remain understudied. Methods The University of Zimbabwe-College of Health Science birth cohort is a prospective cohort study of perinatal HIV and in utero HAART exposure throughout the breastfeeding period in the era of option B+. 600 HIV infected and 600 HIV uninfected pregnant women ≥20 weeks of gestation are being enrolled from four primary health centres in poor high-density residential areas of Harare. Clinical, socio-demographic/economic, nutritional and environmental data and bio-samples including maternal urine, stool, plasma, milk, cord blood, amniotic fluid as well as infant serum, dried blood spots and stool are being collected at enrolment, delivery and longitudinal follow-ups as mother-infant pairs from delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Infants are being assessed for congenital transmission of HIV, hepatitis B/C viruses, cytomegalovirus, syphilis, and growth, neurodevelopment, and immune-dysregulation. Sub-studies are addressing maternal-infant immunometabolomics, latent tuberculosis infection, dysbiosis of the gut microbiome and the effect of maternal stress thereof. The primary end point of this study is infant mortality until two years of age in HEU versus HUU infants. Secondary outcomes include HEU morbidity. Conclusion Our study will provide a comprehensive assessment of risk factors and associated biomarkers for adverse clinical outcomes for HEU infants and ultimately help developing strategies to mitigate effects of HIV, comorbidities and early life HAART exposure on pregnancy outcome and infant health. Trial registration number, date Key words: HIV, Option B+ highly active antiretroviral therapy (HAART), in utero exposure, breastfeeding, antenatal co-morbidities, immune dysfunction, microbiota, genomics, pregnancy outcomes, neurodevelopment infant health.
Status | Active, not recruiting |
Enrollment | 1200 |
Est. completion date | June 30, 2021 |
Est. primary completion date | June 30, 2019 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Female |
Age group | 15 Years and older |
Eligibility | Inclusion Criteria: Consenting pregnant woman of Bantu origin of =15 years of age, at least 20 weeks of gestation at enrolment and planning to deliver at any of the 4 study sites, Kuwadzana, Rujeko, Glenview or Budiriro. Mothers should be willing to be followed together with their babies from delivery, and willing to provide the required data and biological specimens in follow-up visits for two years. Exclusion Criteria: - Presence of severe maternal mental disorders. |
Country | Name | City | State |
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n/a |
Lead Sponsor | Collaborator |
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University of Zimbabwe | Midlands State University, Zimbabwe, National Institute of Health Research, Zimbabwe, University Hospital Inselspital, Berne, University of Cape Town, University of Hamburg, University of Oxford, University of Yaounde, Wellcome Trust |
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* Note: There are 19 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Prevalence of Maternal malnutrition in HIV+ and HIV- | To determine the prevalence of maternal under and overnutrition using BMI and MUAC impact on pregnancy outcomes, infant mortality and morbidity. | At enrollment and 24 months | |
Other | Maternal clinical biochemistry profiles | To assess abnormalities in HIV + and HIV- including lipid profiles, bone, haematological (anemia) and hepatic toxicities associated with exposure to HAART among mothers and infants. | At enrolment and 24 months | |
Other | Infant anaemia and atopic dermatitis | To determine infant non-infectious comorbidities (e.g. anaemia, atopic dermatitis, congenital infections and other conditions) and their impact on mortality and morbidity. | 6 weeks, 6 months and 24 months of age | |
Other | Proportion of Infant abnormal /delayed neuro-cognitive development | To assess delayed neuro-cognitive development using the Denver II tool in HUU, HEU and HEI infants and correlated with socio economic status and infectious diseases. | From 6 weeks,, 10, 14, 24, 36, 48, 96 weeks of age | |
Other | Levels of infants humoural response to EPI vaccines | To determine humoural immune responses to EPI vaccines including antibody levels against measles, tetanus, diphtheria, pertussis, polio and rotavirus) in HUU, HEU and HEI infants. | 6, 48 and 96 weeks of age | |
Other | Infants immune activation and systemic inflammatory biomarkers levels | To determine immune activation and systemic inflammatory biomarkers in HUU, HEU and HEI infants | Delivery, 6, 48 and 96 weeks of age. | |
Other | Infant biomarkers of microbial translocation levels | To determine biomarkers for endothelial dysfunction including microbial translocation in HUU, HEU and HEI infants and association with household hygiene at delivery, 6, 48 and 96 weeks of age. | 6, 48 and 96 weeks of age | |
Other | Normal FBC and biochemistry ranges in pregnancy and after delivery | To determine antenatal reference ranges for MUAC, haemoglobin from FBC analyses, and biochemistry (kidney function, liver function tests, bone, lipid profiles) in mothers with a favourable outcome of pregnancy | Enrollment and 96 weeks. | |
Other | Maternal-infant 16s sequencing profiling | To determine maternal- infant microbiota16S sequencing in pregnancy and relate it to infant immune development and atopy (anti-inflammatory (IL-4, -5, -13) and regulatory cytokines (IL-10, TGF-ß) at delivery, 6 weeks 48 and 96 weeks of age. | Enrollment, delivery, 6 weeks and every 6 months. | |
Other | In-depth maternal-infant microbiota analysis | Bacterial full genome metagenomics shotgun sequencing to identify the microbiota metabolic potential (i.e. bacterial genes present will be done) and mass spectrometry will be performed for analysis of small intestinal content (metabolome). | In pregnancy during breast feeding and after weaning | |
Other | In -depth human milk analysis, including, nutritional values, HAART levels, and herpes viruses and oligosaccharide profiles | Wide range of nutritional profiles and HAART levels spectrometry will be performed for analysis of at least 700 metabolites including amino acids and lipids will be performed in plasma, breast milk and stool samples | Enrollement, 6 weeks 24, 48 and 72 weeks. | |
Other | Viral genetic diversity and evolution | To characterize pathogen genetic diversity including HIV, HBV, HCV, CMV subtypes, prevalent in our study population at time of infection | At enrollment for mothers,earliest available sample for infants and at 2 years | |
Other | Host genetics profiling and trending | To determine host genetic markers for infectious disease susceptibility including human leukocyte antigen (HLA) and killer immunoglobulin like receptor (KIR) gene variants and their association with infection rates of HIV and co-infections in mothers and their infants. | At enrollment for mothers, earliest available sample for infants | |
Primary | Number of infants deaths | On HIV exposed and unexposed infants. | Delivery, 28 day, one and two years | |
Primary | Number of maternal death | HIV infected and HIV uninfected mothers. | two years | |
Secondary | Number of hospitalised Infant morbidity | Comparison of morbidity of HEU vs. HUU infants, defined as impaired growth, immune- and neuro-development and/ or frequent clinically relevant infections | Delivery, 28 days, 6 months, one and two years | |
Secondary | Number of sick clinic visits | Comparison of morbidity of HEU vs. HUU infants, defined as impaired growth, immune- and neuro-development and/ or frequent clinically relevant infections | Delivery, 28 days, 6 months, one and two years | |
Secondary | Number of small for gestational age | To determine any association of maternal HIV infection, HAART exposure. | Birth | |
Secondary | Number of LBW and macrosomia | To determine any association with maternal HIV and HAART exposure. | Birth | |
Secondary | Number of microcephaly | To determine any association with maternal HIV and HAART exposure. | Birth | |
Secondary | Number of apgar score <7 | To determine any association with maternal HIV and HAART exposure. | Birth | |
Secondary | Infant physical growth | To determine any association of HAART exposure in utero and during breast feeding with pregnancy outcome, infant (HUU, HEU, HEI) growth and immune- and neuro-development. | 10 days, 6, 10, 14, 24, 36, 48, 72 and 96 weeks of age | |
Secondary | Proportion of stunted Infants | To determine any association of HAART exposure in utero and during breast feeding with pregnancy outcome, infant (HUU, HEU, HEI) growth and immune- and neuro-development. | 6, 10, 14, 24, 36, 48, 72 and 96 weeks of ag | |
Secondary | Proportion of wasted infants | To determine any association of HAART exposure in utero and during breast feeding with pregnancy outcome, infant (HUU, HEU, HEI) growth and immune- and neuro-development. | 6, 10, 14, 24, 36, 48, 72 and 96 weeks of age | |
Secondary | Number of Infant MUAC below mean 2 standard deviations | To determine any association of HAART exposure in utero and during breast feeding with pregnancy outcome, infant (HUU, HEU, HEI) growth and immune- and neuro-development. | 6, 10, 14, 24, 36, 48, 72 and 96 weeks of age | |
Secondary | Number HIV vertical transmission cases | To determine vertical transmission rates for HIV at birth and within the first 2 years of life and assess risk factors for transmission | 10 day, 6, 24, 48 and 96 weeks | |
Secondary | Maternal HIV incidence | HIV incidence rate among mother sero-negative at enrollment | 24 months | |
Secondary | HAART level in plasma, amniotic fluid and longitudinal breast milk sample | To determine the association between maternal baseline and delivery HAART levels in different compartments and the relation of those to infant HIV transmission, mortality and morbidity. | From pregnancy, at delivery and every 6 months for 2 years | |
Secondary | Level of maternal-infant plasma immune and metabolic dysfunction and in different duration of in utero HAART exposure | To determine the association between antenatal immune dysregulation and infant death, growth and immune responses to vaccines. | From pregnancy, at delivery, 6, 10, 24, and every 6 months for 2 years | |
Secondary | Frequency of mother -infant pairs HIV drug resistance profiles | To determine HIV drug resistance profiles in mother and infants unresponsive to HAART | Earliest possible blood sample and at 24 months | |
Secondary | Proportion of Maternal plasma ,amniotic fluid and breast milk CMV DNAemia | To determine how CMV DNA is influenced by HIV infection, HAART use and as single infection or combined infections in HIV+ and HIV- women and determine the impact on pregnancy outcome and infant cmv vertical transmission | In pregnancy , 10 days, 6, 10 , 14 and 24 weeks. | |
Secondary | Proportion of Maternal positive HBV markers of infection | To determine how HBV infection infections in HIV infected and HIV uninfected women and determine the impact on pregnancy outcome, infant vertical transmission | In pregnancy and 96 weeks | |
Secondary | Proportion of Maternal positive HCV antibodies | To determine HCV infections proportion in HIV positives and negatives women | In pregnancy 6, 24, 48 and 96 weeks | |
Secondary | Prevalence of antenatal syphilis sero-positivity | To determine syphilis infections proportion in HIV positives and negatives and the impact on pregnancy outcome, infant incidence of congenital syphilis infection | In pregnancy 6, 24, 48 and 96 weeks | |
Secondary | Prevalence of antenatal intestinal helminthes infection | To determine the prevalence of helminthes infection using 18s sequencing and correlate with infant development of atopic dermatitis. | From birth , 6, 24, 48 and 96 weeks of age |
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